European Thyroid Journal最新文献

Objective: Thyrotropin receptor antibodies (TRAbs) are central to Graves' disease management, but their long-term kinetics after total thyroidectomy is poorly defined. We aimed to describe long-term TRAb trajectories and identify predictors of decline using clinically relevant thresholds.

Methods: TRAb levels were measured serially in 1,516 patients after total thyroidectomy. Primary outcomes were time to TRAb < 10 and <2 IU/L, corresponding to a pragmatic fetal-risk threshold and assay negativity, respectively. Clinical factors (age, sex, body mass index, smoking, preoperative TRAb, and thyroid weight) were evaluated using Kaplan-Meier analyses and multivariable logistic regression.

Results: TRAb levels declined rapidly, with median values falling below 10 IU/L within 2 years. Among patients with preoperative TRAb ≥ 10 IU/L, 84.8% reached <10 IU/L and 60.1% reached <2 IU/L within 5 years. In multivariable models, younger age, lower preoperative TRAb, and smaller thyroid weight independently predicted earlier decline, whereas sex, body mass index, and smoking did not.

Conclusions: In this large post-operative cohort, younger age emerged as an independent predictor of accelerated TRAb decline after total thyroidectomy. Total thyroidectomy yields sustained TRAb decline and may promote immunological remission, particularly in younger patients, by removing the antigenic source before the establishment of long-lived plasma cells. These findings highlight age as a key determinant of TRAb kinetics and provide timelines for counselling and follow-up. Surgery may be especially valuable when a timely TRAb decline is required, such as in younger patients planning pregnancy or those with orbitopathy or antithyroid drug refractoriness.

Background: Paediatric and young adult differentiated thyroid carcinoma (DTC) often presents at an advanced stage but carries an excellent prognosis. While age-related genomic differences from adult DTC are recognized, it remains unclear whether outcomes are driven by age or tumour biology.

Methods: We analysed a multi-institutional cohort of 363 patients aged 0-25 years who underwent molecular testing and surgical management. Age was categorized using cutoffs at ≤8, 9-14, 15-18, and 19-25 years). The primary endpoint was disease status at last follow-up, categorized according to American Thyroid Association (ATA) response criteria. Multivariable ordered logistic regression was used to test the independent prognostic effect of somatic driver mutations while adjusting for age, sex, and follow-up duration.

Results: Distinct age-related patterns of oncogenic drivers were observed: RET and NTRK1/3 fusions were predominant in younger patients, BRAF V600E was most frequent in adolescents, and RAS mutations were enriched in young adults. After adjustment, driver mutations independently predicted long-term outcomes. NTRK1/3 fusions (aOR 5.29, 95% CI 1.77-15.79), BRAF V600E (aOR 3.45, 95% CI 1.37-8.70), and RET fusions (aOR 3.34, 95% CI 1.13-9.90) were associated with significantly higher odds of a non-excellent outcome. Conversely, RAS mutations showed a favourable trend, and all DICER1-mutant cases achieved excellent outcomes. While prognosis steadily improved with age, mutation status remained the dominant factor determining outcomes.

Conclusion: Somatic drivers offer prognostic insights independent of age in paediatric and young adult DTC, establishing a molecular framework for precision risk stratification that complements traditional clinical staging and age-based assessments.

Monoethyl phthalate, a major metabolite of phthalate esters, is commonly found in the environment and has been linked to an increased risk of thyroid cancer. This study uses network toxicology to predict molecular initiators involved in monoethyl phthalate-induced thyroid cancer and to explore causal relationships and biological mechanisms. We identified 72 common candidate genes of monoethyl phthalate and thyroid cancer from PubChem, CTD, STITCH, GeneCards, and OMIM databases and selected 48 genes for Mendelian Randomization (MR) analysis. Using the IEU database and employing expression quantitative trait loci (eQTLs) as instrumental variables (IVs), we executed MR analysis to identify 10 monoethyl phthalate-related targets with potential causal relationship to thyroid cancer. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted that the biological processes primarily involve intracellular receptor signaling, response to estradiol, nuclear receptor activity, ligand-activated transcription factor activity, and cancer-related signaling pathways, such as the cell cycle and tryptophan metabolism. A protein-protein interaction (PPI) network identified interactions between 7 of these genes, revealing 5 core genes (ESR1, SKP2, CASP8, ARNT, and CDKN1B) as key candidate mediators in monoethyl phthalate-induced thyroid cancer. Molecular docking simulations suggested potential direct interactions between monoethyl phthalate and their protein products. Our findings propose 10 genes as potential mediators of monoethyl phthalate-induced thyroid cancer, with ESR1, SKP2, CASP8, ARNT, and CDKN1B highlighted as core factors potentially involved in thyroid cancer pathogenesis.

European iodine fortification programmes are heterogeneous and in some countries ineffective. A key problem with iodine nutrition is the low awareness of iodine deficiency-related risks common in the general population and among women of reproductive age. The major objective of EUthyroid2 is to improve the low awareness of IDD risks in adolescents and young women. The aim is to identify best practice models for accessing and disseminating information to increase awareness and improve iodine status, thereby establishing a foundation for young women to improve their own thyroid function, their general health and that of their offspring. To achieve this, EUthyroid2 will build on existing infrastructures and expertise established by the consortium during the initial EUthyroid project. All interventions tested will be tailored to specific regions and populations. EUthyroid2, by identifying the most effective intervention tools, will establish a solid foundation for paving the way for future national awareness campaigns.

Purpose: We examined the effect of selenium vs placebo on remission rate and quality of life (QoL) in the Graves' selenium supplementation (GRASS) trial (ID: NCT01611896).

Methods: Double-blinded, placebo-controlled, multi-centre trial in individuals with newly diagnosed Graves' hyperthyroidism randomised to daily supplementation with 200 μg selenium or placebo tablets during 24-30 months, depending on the timing of antithyroid drug (ATD) withdrawal. The primary outcome was the proportion of participants with non-remission, defined as receiving ATD or remaining hyperthyroid (thyroid stimulating hormone <0.1 mIU/L) during the last 12 months of the intervention period or referral to ablative therapy (radioactive iodine or surgery). QoL was serially assessed by the thyroid-related patient-reported outcome ThyPRO and compared with previously collected norm data.

Results: Between Dec 7th 2012 and Dec 3rd 2018, 430 participants with Graves' hyperthyroidism were recruited. Non-remission was observed in 114 (53.3%) participants in the placebo group and 118 (54.6%) in the selenium group (OR = 1.0 (95% CI: 0.7-1.5); P = 0.98). There was no beneficial effect of selenium, as compared with placebo, on any ThyPRO scale. The participants' QoL at the end of the study was comparable to that of the general population sample. Thyrotropin receptor antibody levels were similar in the groups at the 18-month and end-of-study follow-up visits.

Conclusion: In individuals with newly diagnosed Graves' hyperthyroidism, daily supplementation with selenium did not have any effects compared with placebo as add-on to standard antithyroid drugs. The GRASS trial findings do not support the use of selenium supplementation in Graves' hyperthyroidism.

Long non-coding RNAs (lncRNAs) are untranslated RNA molecules that regulate gene expression through diverse mechanisms, acting as scaffolds, guides, decoys, or signals. In thyroid cancer, the most prevalent endocrine malignancy, lncRNAs are increasingly recognized as key contributors to tumor development and progression. Elucidating these molecular mechanisms is essential for advancing diagnostic, prognostic, and therapeutic strategies. This review highlights major lncRNAs implicated in thyroid cancer, categorizing them as upregulated/oncogenes or downregulated/tumor suppressors, and describing their mechanisms of action and interactions. LncRNAs are typically expressed at low levels and tightly regulated to preserve normal cell behavior. In thyroid cancer, they serve as crucial regulators of oncogenesis, frequently acting as competing endogenous RNAs that influence key signaling pathways. While most studies focus on miRNA sponging, other mechanisms are underexplored. Circulating lncRNAs offer potential for non-invasive diagnostics, and several lncRNAs show promise as therapeutic targets. Thus, continued research into the diverse functions of lncRNAs is vital to fully harness their clinical potential in thyroid cancer.

This review explores the role of BRAF V600E in thyroid cancer with emphasis on its debated prognostic value, notable molecular heterogeneity, and opportunities as a therapeutic target. BRAF V600E, the most common oncogenic driver in papillary thyroid carcinoma, activates the MAPK pathway and suppresses genes involved in iodine metabolism and differentiation. While linked to adverse features and outcomes such as extrathyroidal extension, lymph node metastasis, recurrence, and mortality, its utility as an independent prognostic marker remains controversial. In solitary intrathyroidal tumors (1-4 cm) and low-risk microcarcinomas, BRAF V600E testing may help refine surgical decisions, though evidence is inconsistent, particularly for tumors <2 cm. The mutation also contributes to radioactive iodine (RAI) refractoriness, but not all BRAF-mutant tumors behave similarly. Transcriptomic and genomic heterogeneity - including differences in thyroid differentiation score, genetic co-alterations and miRNA signatures - modulates treatment response. Targeting BRAF V600E has led to novel therapeutic strategies. Selective BRAF and MEK inhibitors - including vemurafenib, dabrafenib, and selumetinib - have demonstrated efficacy in advanced thyroid cancers. The combination of dabrafenib and trametinib is FDA approved for BRAF V600E-mutant anaplastic thyroid carcinoma based on its significant survival benefits. Moreover, due to its histology-agnostic approval for solid tumors with BRAF V600E mutations, this regimen is now also indicated for papillary and poorly differentiated thyroid cancers. In addition, redifferentiation strategies using MAPK inhibitors to restore RAI avidity have shown promise, particularly in selected patients. These advances highlight the need to contextualize BRAF mutation status within a broader molecular and clinical framework to guide personalized, effective treatment strategies.

Introduction: Thermal ablation (TA), including radiofrequency (RFA) and microwave ablation (MWA), is a widely used, minimally invasive alternative to surgery for benign thyroid nodules. While transient, self-limited thyrotoxicosis is a recognized effect of the procedure, the onset of Graves' disease (GD) post-TA remains exceedingly rare and poorly characterized.

Case reports: We report three cases of new-onset GD occurring 3-10 months after RFA or MWA, identified among more than 500 patients treated at our tertiary care Endocrinology Unit. All patients were female and had undergone TA for cytologically benign nodules. Two had a documented history of thyroid autoimmunity. At diagnosis, all three exhibited suppressed TSH, elevated thyroid hormone levels, and positive anti-TSH receptor antibodies (TRAb). None had been tested for TRAb before treatment. One case occurred during pregnancy and was managed with propylthiouracil; the others received antithyroid treatment with methimazole.

Conclusion: Although rare, GD may develop following TA, likely through immune activation triggered by thyroid tissue injury in genetically predisposed individuals. Routine TRAb screening before TA is not currently justified; however, clinical awareness is essential to distinguish transient post-ablation thyrotoxicosis from true GD and to ensure timely initiation of antithyroid therapy when appropriate. Despite these rare cases, the overall incidence remains very low, confirming the excellent safety profile of TA for benign thyroid nodules.

Objective: Dysthyroid optic neuropathy (DON) is a severe complication of thyroid eye disease (TED) with limited early detection methods. This study aimed to investigate the clinical characteristics of patients with TED who developed DON and to establish a predictive model for early identification of high-risk cases.

Methods: Herein, 257 TED patients were prospectively included, of whom 68 (26.5%) developed DON. All patients were divided into derivation and validation cohorts, and Least Absolute Shrinkage and Selection Operator (LASSO) regression and logistic regression analyses were applied to identify clinical factors and construct a prediction model.

Results: In the derivation cohort (185 TED patients), 49 (26.5%) developed DON. DON patients showed significantly higher prevalence of pretibial myxedema (PTM) (22.4 vs 5.9%, P = 0.001), diabetes mellitus (18.4 vs 7.4%, P = 0.029), older age (58.04 ± 11.30 years vs 47.99 ± 10.65 years, P < 0.001), higher CAS (5 vs 4, P < 0.001), elevated triglyceride (TG) levels (1.44 mmol/L vs 1.15 mmol/L, P = 0.042), and lower visual functioning (VF) (43.75 vs 62.50, P < 0.001). LASSO regression analysis identified age, PTM, TG, VF, and CAS as independent predictors of DON. The developed nomogram presented AUCs of 0.853 (95% CI: 0.792-0.914) and 0.856 (95% CI: 0.762-0.950) in the derivation and validation cohorts, respectively.

Conclusions: Altogether, the findings of this study identify advanced age, elevated CAS, increased TG, lower VF, and PTM as significant predictors of DON in patients with TED. The proposed nomogram offers a practical clinical tool for risk stratification, providing clinicians with an approach for individualized risk assessment and timely therapeutic intervention.